[STDs] Atlas of Reactive Arthritis

These are the images, diagnosis and treatment of cases the disease caused by Reactive Arthritis.

Reactive arthritis∗ is classically described as a triad of rheumatoid factor–negative arthritis, urethritis or cervicitis, and mucocutaneous inflammatory lesions, including conjunctivitis and a characteristic dermatitis. The syndrome results from an aberrant immune response after an initial triggering event, including genital infection with Chlamydia trachomatis and perhaps Neisseria gonorrhoeae, as well as enteric pathogens, including Salmonella, Shigella, Campylobacter, and Yersinia. In addition to the roles of chlamydial urethritis and cervicitis as triggering events, nongonococcal urethritis (NGU) and mucopurulent cervicitis are common manifestations of reactive arthritis, presumably due to an immunologic mechanism. Limited forms of the syndrome, such as isolated arthritis, are common at presentation, but most patients eventually develop mucocutaneous or ocular manifestations.

Reactive arthritis is clinically and pathologically related to other spondyloarthropathies like ankylosing spondylitis and psoriatic arthritis. Up to 90% of affected persons have the histocompatibility locus A (HLA) B27 haplotype. Reports of C. trachomatis antigens, DNA, and occasionally viable organisms in synovial tissues suggest a role of direct dissemination of the triggering infection in the pathogenesis of reactive arthritis, or in sustaining chronic arthritis in some patients. A proposed new terminology defines “Chlamydia-induced spondyloarthropathy” as a specific subset of reactive arthritis. In further support of persistent infection in pathogenesis, recent research suggests that a 6-month course of combination antibiotics (azithromycin or doxycycline, plus rifampin) helps control symptoms in patients with chronic forms of the syndrome.

Sporadically occurring reactive arthritis usually is triggered by genital infection, most frequently chlamydial NGU or cervicitis. Gonorrhea probably triggers some cases, which may present as “postgonococcal arthritis” and is distinct from the arthritis of disseminated gonococcal infection. Overt epidemics of reactive arthritis have occurred in populations with especially high prevalences of the HLA-B27 haplotype, as in Scandinavia, sometimes following outbreaks of enteric infection such as shigellosis or Yersinia enteritis. Differentiating reactive arthritis from gonococcal arthritis is sometimes difficult, especially in sexually active persons who lack the characteristic skin lesions of either syndrome. Reactive arthritis usually is transient or causes modest functional limitation, but sometimes becomes disabling due to prolonged severe arthritis, secondary amyloidosis, or other complications.

EPIDEMIOLOGY

Incidence and Prevalence

• Among the most common causes of arthritis in young adults, but accurate statistics not available

Transmission

• Depends on triggering infection

• Person-to-person transmission of Chlamydia-linked reactive arthritis has been reported

Age

• All ages are susceptible

• Most cases occur in sexually active age groups

• Cases triggered by enteric infections have occurred in children as well as adults

Sex

• Modest male predominance, with male-female ratio 1:1 to 2:1

• Previously reported male-female ratios as high as 10:1 probably were due to reporting bias or underdiagnosis of cervicitis in women with seronegative arthritis

Sexual Orientation

• No special predilection

• MSM may be at increased risk due to elevated frequency of sexually acquired enteric infections

Other Risk Factors

• Frequency of reactive arthritis has been reported to be 20–35% following chlamydial or enteric infection in persons with HLA-B27 haplotype

• HIV-infected persons may be at elevated risk

HISTORY

Incubation Period

• Typically 1–4 weeks after onset of trigger infection

Symptoms

• Pain, swelling, and limited mobility of involved joints

° Usually 1–3 joints involved in initial episode

° Most commonly involved sites are heel, toes, lumbosacral spine, knee, or ankle, but any joint can

be affected 

• Symptoms of urethritis or cervicitis often are present
• Sometimes recent diarrhea or other symptoms of enteric infection
• Fever and other systemic symptoms may occur but usually are mild or absent
• Skin rash, symptoms of conjunctivitis, and oral ulcers (usually painless) may develop early or late

PHYSICAL EXAMINATION

Trigger Infection

• Signs of urethritis, cervicitis, or gastrointestinal infection

Arthritis

• Inflammatory signs of one or more joints

• Synovial effusion may be present when large joints are involved (e.g., knee, ankle)

• Tenderness often maximal at tendon insertion sites (entheses) (hence the rheumatologic classification of reactive arthritis as an “enthesopathy”)

• Diffuse synovitis of one or more fingers or toes (“sausage digit”) is uncommon but considered highly specific for reactive arthritis

• Sacroiliac joint tenderness may be present

Mucocutaneous Lesions

• Keratoderma blennorrhagica

° Hyperkeratotic lesions with erythematous base, usually on extremities, sometimes in clusters

° Resembles psoriasis clinically and histologically

° Often involves palms and soles

° May mimic secondary syphilis

° Pustular component sometimes present

• Circinate balanitis: Superficially erosive dermatitis of the glans penis in uncircumcised men, often with a “geographic” morphology, is pathognomonic

• Conjunctivitis often present, usually bilateral

• Sometimes superficial ulcers of oral mucosa

Other Manifestations

• Fever, malaise, other constitutional symptoms; usually limited to severe cases

• Uncommon findings (<1% of cases) include iritis, uveitis, heart block or other cardiac arrhythmias, and focal neurological signs

• Amyloidosis is a rare complication of chronic cases

LABORATORY EVALUATION

• No definitive laboratory test exists

• Evaluate as for NGU and cervicitis (see Chaps. 15, 18), including NAATs for C. trachomatis and N. gonorrhoeae 

• If synovial effusion present, aspirate for bacterial culture, leukocyte count, and analysis for crystals

• Blood cultures for to evaluate for bacterial septic arthritis, including gonococcal arthritis

• If current or gastrointestinal manifestations, test stool for enteric pathogens

• Serum rheumatoid factor test

• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) may be useful to follow clinical

course and response to therapy

• HLA typing may help confirm diagnosis

• Several weeks after onset, x-ray lumbosacral spine; many patients develop radiological signs of

sacroiliitis, whether or not there are symptoms of spinal involvement

DIAGNOSTIC CRITERIA

• American Rheumatism Association definition of reactive arthritis: Rheumatoid factor–negative arthritis

>1 month in duration, associated with urethritis or cervicitis

• Exclude other causes of arthropathy, especially septic arthritis, DGI, and gout and other crystalinduced arthritis

• Synovial fluid usually has high cell count (>20,000/mm3) with predominant PMNs

• HLA-B27 haplotype helps confirm diagnosis

• If DGI or septic arthritis cannot be excluded, consider therapeutic trial with IV antibiotics

TREATMENT

• Treat trigger infection with appropriate antibiotic, such as azithromycin or doxycycline for chlamydial infection or NGU

• Mainstay of arthritis therapy is nonsteroidal anti-inflammatory drugs; aspirin and corticosteroids usually are ineffective

• Biological agents such as infliximab or adalumimab may have a role in management of chronic, disabling cases

• Azithromycin or doxycycline, plus rifampin, for 6 months may result in clinical improvement in some patients with chronic, disabling reactive arthritis; confirmatory research necessary

• Manage in consultation with a rheumatologist or other expert

PREVENTION

• Manage sex partners and report cases as dictated by triggering infection 

17–1. Reactive arthritis: circinate balanitis.

CASE 1

Patient Profile Age 27, surgery resident

History Low back pain and intermittent pain in both heels for 4 weeks; rash involving penis and feet for 3 days; pain and swelling of right knee for 1 day; no genital symptoms, diarrhea, fever, or other symptoms; last sexual exposure 2 months earlier

Examination Effusion and reduced range of motion of right knee; tenderness at Achilles tendon insertion sites of both heels; geographic eruption of glans penis and underside of foreskin; hyperkeratotic inflammatory skin lesions of lower extremities; no urethral discharge; 50 mL of cloudy synovial fluid aspirated from knee

Differential Diagnosis Reactive arthritis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, disseminated gonococcal infection

Laboratory Gram-stained urethral smear showed many PMNs without GND; urethral swabs were cultured for C. trachomatis (positive) and N. gonorrhoeae (negative); synovial fluid contained 42,000 leukocytes per mm3 with 90% PMNs, no crystals, negative Gram stain and culture; rheumatoid factor and VDRL negative; complete blood count and chemistry panel normal; ESR 43 mm/h; HLA-B27 positive

Diagnosis Reactive arthritis triggered by C. trachomatis

Treatment Doxycycline 100 mg orally bid for 7 days; indomethacin 150 mg orally tid

Partner Management Referred for examination and treatment for chlamydial infection

Comment The patient had prompt symptomatic response, permitting cessation of indomethacin after 2 months. His most recent sex partner was referred, found to have cervical chlamydia, and treated. Subsequently he had persistent but nonlimiting low back pain, and sacroiliac radiographs after 1 year showed hypertrophic changes and narrowed joint spaces. Currently, naproxen or other nonsteroidal anti-inflammatory drug would normally be used in lieu of indomethacin.

17–2. Reactive arthritis: keratoderma blennorrhagica.  

17–3. Severe plantar keratoderma blennorrhagica in chronic reactive arthritis. 

Compare with secondary syphilis  

17–4. Cutaneous lesions of the knee consistent with keratoderma blennorrhagica
or psoriasis in a woman with acute spondyloarthritis. The patient was the sex
partner of a man with NGU, but lacked evidence of C. trachomatis, cervicitis, or
other lower genital tract infection and was HLA-B27 positive. Reactive arthritis
and psoriatic arthritis could not be differentiated.  

17–5. Diffuse dactylitis (“sausage toe”) of third digit in a patient with reactive arthritis  

REFERENCES

H. Hunter Handsfield, MD, Color Atlas & Synopsis of Sexually Transmitted Diseases, Third Edition.